Pharmacological Enhancement of Autophagy Induced in a Hepatocellular Carcinoma Cell Line by High-LET Radiation
Fiche publication
Date publication
février 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr JUNG Alain, Pr NOEL Georges
Tous les auteurs :
Altmeyer A, Jung AC, Ignat M, Benzina S, Denis JM, Gueulette J, Noel G, Mutter D, Bischoff P
Lien Pubmed
Résumé
The aim of the present study was to determine the cytotoxic consequences of high-linear energy tran, fer (LET) irradiation in the presence of oxaliplatin on hepatocellular carcinoma (HCC) cells in vitro. We attempted to correlate the induction of apoptosis and autophagy with the formation of DNA double-strand breaks (DSBs). SK-Hepl cells were irradiated by 65 MeV neutrons in the presence of oxaliplatin and/or the poly(ADP-ribose) polymerase (PARP) inhibitor PJ34. DSBs were measured by the formation of gamma H2AX foci. Results show that in SK-Hepl cells exposed to fast neutrons in the presence of oxaliplatin, DSBs occurred and persisted with time after irradiation. While apoptosis remained low in co-treated cells, autophagy was considerably increased after irradiation and augmented by the addition of oxaliplatin. Thus, autophagic cell death appears to play a prominent role in the cytotoxicity of the combined treatment and may be linked to the generation of heavy damage to DNA.
Référence
Anticancer Res. 2010 Feb;30(2):303-10.